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Immunology PY2 > Lecture 6: Complement > Flashcards

Lecture 6: Complement Flashcards

1
Q

the complement system consists of approximately ___ pre-made proteins and membrane components

A

50

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2
Q

the complement system is activated by sequential _____ of substrates that results in a ____ reaction

A

proteolytic cleavage; cascade

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3
Q

what are 4 functions of the complement system?

A
  1. lyse target cells
  2. promote phagocytosis (opsonization)
  3. induce inflammatory responses (anaphylatoxins)
  4. clear immune complexes (phagocytes)
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4
Q

what are the 3 pathways of activation of the complement system?

A
  1. classical
  2. alternative
  3. lectin
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5
Q

what is the only stage of the cascade that differs between the classical, alternative and lectin pathways?

A

the initiation

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6
Q

once you arrive at ___, the cascade is the same for all three complement pathways

A

C3 convertase

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7
Q

in the complement system, all roads lead to the C3 convertase; which lyses C3 into ___ and ___

A

C3a and C3b

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8
Q

C3 is also known as ____ and is the ___ (active or inactive) form and is cleaved into C3a and C3b which are the ____(active or inactive) form

A

zymogen; inactive; active

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9
Q

the C3b fragment complexes with ____ to create C5 convertase

A

C3 convertase (C4b2A or C3bBb)

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10
Q

the C3a fragment has what role?

A

it is an anaphylatoxin (driver of inflammation)

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11
Q

if C5 convertase complexes with C3bBb, what pathway will be taken>

A

alternative

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12
Q

what is the role of the C5b fragment?

A

binds to the cell membrane to permit formation of the membrane attack complex (MAC)

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13
Q

what is the role of the C5a fragment?

A

anaphylatoxin (driver of inflammation)

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14
Q

what is the role C6 in the MAC complex?

A

stabalizes the C5b

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15
Q

what is the function of the C7 in the MAC?

A

binds C5bC6 and inserts into the cell membrane

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16
Q

what is the function of C8 in MAC?

A

binds C5bC6C7 and creates a pore in the cell membrane

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17
Q

what is the function of C9 in the MAC?

A

there are typically 10-15 per MAC and they bind the C5cC6C7C8 and make a large pore in the membrane

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18
Q

what is the role of the alternative complement pathway?

A

involved in innate immunity and functions in the absence of specific antibody

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19
Q

what are 2 mechanisms for activation of the alternative complement pathway?

A
  1. spontaneous hydrolysis of C3 (tickover or fluid-phase C3 convertase)
  2. by pathogens or other serum proteins (like clotting cascade components)
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20
Q

activation of the classical pathway requires one or more ___

A

antibody-antigen complexes containing IgM or IgG binding to C1q

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21
Q

what causes the activation of the lectin pathway?

A

binding of mannose-binding lectin (MBL) to mannose residues and carbohydrates on certain microbes

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22
Q

what is MBL (mannose binding lectin)?

A

a serum protein

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23
Q

does the lectin complement pathway depend on antobodies?

A

no

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24
Q

explain the lectin complement pathway

A

MBL-associated serine proteases (MASP-1 and MASP-2) bind MBL on the microbe surface, forming a complex that is able to cleave C4 and C2 to make C4b2a = C3 convertase

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25
Q

what are 3 examples of innate defence complement activity?

A
  1. membrane attack complex-mediated lysis of micribes (C5b-C9)
  2. opsonization (C3b and IgG)
  3. introduction of inflammation and chemotaxis by anaphylatoxins
26
Q

with anaphylatoxins, activation of the inflammatory response by C3a and C5a occurs via ___ and _____

A

chemoattraction and mast cell degranulation

27
Q

what are the 4 biological functions of complement?

A
  1. cell lysis by MAC
  2. opsonization
  3. anaphylatoxins
  4. virus neutralazation
28
Q

what does the complement system use for cell lysis?

A

MAC

29
Q

what does the complement system use for opsonization and phagocytosis?

A
  1. opsonization: C3b, iC3b and C4b promote phogocytosis

2. C5a activates phagocytes

30
Q

clearance of particulate immune complexes occurs by what process?

A

phagocytosis

31
Q

soluble immune complex clearance is caused by an interaction of ___ and ___ on red blood cells

A

C3b and CR1

32
Q

what molecules are anaphylatoxins?

A

C3a, C4a and C5a

33
Q

which anaphylatoxins are chemotractant for granulocytes and monocytes and also cause platelet aggregation?

A

C3a and C5a

34
Q

how does the complement system cause virus neutralization?

A

by aggregation, opsonization and lysis (of envelopoed viruses) to reduce infectivity

35
Q

what is the function of the CR1?

A

clearnace of immune complexes, enhancement of phagocytosis, regulation of C3 breakdown

36
Q

what is the function of CR3?

A

binding to adhesion molecules on leukocytes, facilitates extravasation; iC3b binding enhances opsonization of immune complexes

37
Q

what is the function of CR4?

A

ic3b mediated phagocytosis

38
Q

what is the function of C3aR?

A

induces degranulation

39
Q

what is the function of C5aR?

A

induces degranulation, chemoattraction, acts with IL-1B and or TNF-a to induce acute phase response; induces respiratory burst in neutrophils

40
Q

The ____ nature of many complement components ensures that only appropriate targets such as invading micribes are attacked by the complement system

A

labile (easily broken down)

41
Q

the complement system is subject to ____ which competes against complement in order to prevent excessive activation

A

active regulation

42
Q

t/f active regulation can happen at several points in the compliment pathway

A

t

43
Q

what are the 5 approaches to regulating complement?

A
  1. dissociation of C1 components
  2. factor 1 cofactor activity
  3. decay-accelerating activity for C3 convertase
  4. inhibition of lysis
  5. cleavage of anaphylatoxins
44
Q

what is the function of C1 inhibitor (C1INH)?

A

induces dissociation and inhibition of C1r2s2 from C1q; serine protease inhibitor

45
Q

is C1 inhibitor a fluid phase or a membrane protein?

A

fluid phase

46
Q

which pathways are affected by C1 inhibitor?

A

classical and lectin

47
Q

what is the function of decay-accelerating factor (DAF) CD55?

A

accelerates the dissociation of C4b2a and c3bBb C3 convertase

48
Q

is DAF fluid phase or membrane protein?

A

membrane bound

49
Q

what pathways are affected by DAF?

A

classical, alternative and lectin (all of them)

50
Q

what is teh function of factor H?

A

blocks the formation of, or quickens the dissociation of C3bBb C3 convertase

51
Q

what pathways are affected by factor H?

A

alternative

52
Q

is factor H a membrane or fluid phase protein?

A

soluble

53
Q

what is teh function of factor I?

A

serine protease; cleaves C4b and C3b using cofactors

54
Q

what pathways are affected by factor I?

A

classical, alternative, and lectin (all of them)

55
Q

what is the function of protectin (CD59)?

A

binds C5b678 on host cells, blocking binding of C9 and the formation of the MAC complex

56
Q

what pathways are affected by protectin?

A

all

57
Q

is protectin membrane or soluble protein?

A

membrane

58
Q

what is the function of the carbopeptidases N, B and R ?

A

cleave and inactivate the anaphylatoxins C3a and C5a

59
Q

what pathways are affected my carboxypeptidases?

A

all that produce anaphylatoxins

60
Q

are carboxypeptidases soluble or membrane proteins?

A

soluble

61
Q

t/f the alternate and lectin pathways need to have previous exposure to the pathogen to activate, while the classical pathway does not

A

t

Immunology PY2 (20 decks)

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